Diaphragmatic Activity Research Articles

Functional Impact of nTS Glutamate Stress on Respiration in an Alzheimer’s Disease Model

Alzheimer’s disease (AD) is closely associated with obstructive sleep apnea (OSA). Such hypoxic insults trigger glutamate release of chemoafferents into the nucleus tractus solitarii (nTS), an important upstream center of the chemoreflex. Potential alterations of glutamate handling in the nTS may lead to the respiratory dysfunction seen in AD patients. Using the streptozotocin (STZ)-induced rat model — an effective proxy for human AD — we studied the functional consequences of nTS glutamate stress on respiration. STZ-AD was induced in 6-week-old male Sprague Dawley rats via intracerebroventricular injections of 2 - 2.25 mg/kg STZ. After two weeks, EMG recordings of diaphragm activity served as surrogate for respiratory responses to glutamate microinjections (20 nL of 40 mM) into the caudal nTS. In a subset of rats, chemoafferent terminals were labeled with the fluorescent tracer DiI to permit patch clamp recordings of identified 2nd order nTS neurons participating in the chemoreflex loop. Evoked glutamatergic excitatory postsynaptic currents (TS-EPSCs) were generated via tractus solitarii stimulation at frequencies (10 - 40 Hz) typical for afferent discharge during hypoxia. Acute glutamate injections into the caudal nTS increased respiratory frequency by 15 - 20 breaths per minute. The response magnitude was similar between CTL and STZ-AD animals. Excitatory stress with repeated glutamate injections (5 min. apart) evoked a reliable respiratory response in CTL that slowly declined to ~65% from its maximum over the course of 10 injections. In contrast, the decline of respiratory response in STZ-AD was more pronounced and occurred significantly earlier than in CTL, indicating altered glutamate handling in the caudal nTS of STZ-AD rats. Next, we used patch clamp electrophysiology to analyze increased glutamate release of chemoafferents onto 2nd order nTS neurons. High frequency stimulation of chemoafferents induced a successive depression of TS-EPSC amplitude in nTS neurons. TS-EPSC depression was significantly stronger in STZ-AD and may be due to altered glutamate handling at the synapse. Western Blot analysis of STZ-AD brainstem tissue including the nTS revealed a significant increase in glial fibrillary acidic protein (GFAP) expression and a decrease of excitatory amino acid transporters (EAATs) expression, suggesting astrocyte involvement in compromised nTS glutamate handling in STZ-AD. In summary, the STZ-AD model showed reduced respiratory responses to glutamate stress in the caudal nTS. The altered stress response may come from enhanced depression of TS-EPSC amplitude at nTS neurons in the chemoreflex. Altered astrocytic glutamate removal from the synaptic cleft may contribute to TS-EPSC depression. Together, altered glutamate handling in a respiratory brainstem center may contribute to OSA in AD patients. NIH R15AG065927 (TDO & DO), KCOM Biomedical Graduate Program (RKT &TDO), ATSU Research Support (SKRC). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Acute stress augments obstructive apneas and related O2-desaturations in urethane-anesthetised rats via disruption of cholinergic modulation

Obstructive sleep apnea (OSA) is a multifactorial respiratory disorder affecting nearly 1 billon of adults worldwide. Anomalies in respiratory control during sleep contribute to airway obstructions and recurrent desaturations; however, the origins of the problem are not well known. Stress disrupts brain function and increases the risk of OSA co-morbidities, including hypertension and obesity. Because, hypothalamic structures regulating the stress response also project to medullary areas regulating cardiorespiratory function and airway motor control, we hypothesised that exposure to a single stress session is suffcient to induce cardiorespiratory disturbances associated with OSA. Experiments were performed in urethane-anesthetised rats; this approach allows sleep-like brain state alternations with significant reductions in upper airway (genioglossus; GG), but not diaphragmatic (DIA), muscle tone during the transition from NREM-like to REM-like states. Adult male rats were either subjected to a 90 min session of immobilisation stress (n = 21) or handled briefly by the experimenter (n = 18). 24h later, rats were anesthetised (urethane, 1.6 g/kg; i.v.) and instrumented to monitor DIA and GG EMG. O2 saturation was measured by pulse oximetry (S pO2). Blood pressure was measured by an arterial catheter. Rats were placed in a supine position and respiratory airflow was measure by a temperature probe near the nares. Obstructive apneas were identified by the absence of airflow in the presence of DIA activity with a S pO2 drop greater than 3%. Stress did not affect distribution of sleep-like states or the state-related changes in phasic GG activity. However, stress augmented the incidence of obstructive apneas (0.5 vs 2.2 events/h; p = 0.05) and doubled the severity of desaturations associated with apneas (-6% vs -12% drop; p = 0.03). Pre-treatment with atropine (0.5 mg/kg) reduced obstructive apneas (drug effect: p = 0.04). Atropine blocked apnea-related O2 desaturations in stressed but not controls (apnea x stress x atropine: p = 0.04). Atropine treatment augmented GG activity; this effect was greater in NREM-like state, especially in stressed rats (atropine x state x stress: p = 0.05). We conclude that, in urethane anesthetised rats, stress disrupts cardiorespiratory control in ways that favor significant obstructive apneas. Disruption of cholinergic modulation of GG activity and cardiovascular function likely contributes to this process. These data point to an important factor in the onset of OSA. While the frequency of apneas was modest we propose that recurrent exposure to stressors or more significant events will worsen the condition over time. Supported by the Canadian Institutes of Health Research and the Foundation of the Québec Heart & Lung Institute. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Ampakines increase diaphragm activation following mid-cervical contusion injury in rats

Ampakines are positive allosteric modulators of AMPA receptors. We hypothesized that low-dose ampakine treatment increases diaphragm electromyogram (EMG) activity after mid-cervical contusion injury in rats. Adult male and female Sprague Dawley rats were implanted with in-dwelling bilateral diaphragm EMG electrodes. Rats received a 150 kDyn C4 unilateral contusion (C4Ct). At 4- and 14-days following C4Ct, rats were given an intravenous bolus of ampakine CX717 (5 mg/kg, n = 10) or vehicle (2-hydroxypropyl-beta-cyclodextrin; HPCD; n = 10). Diaphragm EMG was recorded while breathing was assessed using whole-body plethysmography. At 4-days, ampakine administration caused an immediate and sustained increase in bilateral peak inspiratory diaphragm EMG bursting and ventilation. The vehicle had no impact on EMG bursting. CX717 treated rats were able to increase EMG activity during a respiratory challenge to a greater extent vs. vehicle treated. Rats showed a considerable degree of spontaneous recovery of EMG bursting by 14 days, and the impact of CX717 delivery was blunted as compared to 4-days. Direct recordings from the phrenic nerve at 21–24 days following C4Ct confirmed that ampakines stimulated bilateral phrenic neural output in injured rats. We conclude that low-dose intravenous treatment with a low-impact ampakine can enhance diaphragm activation shortly following mid-cervical contusion injury, when deficits in diaphragm activation are prominent.

V2a neurons restore diaphragm function in mice following spinal cord injury

The specific roles that different types of neurons play in recovery from injury is poorly understood. Here, we show that increasing the excitability of ipsilaterally projecting, excitatory V2a neurons using designer receptors exclusively activated by designer drugs (DREADDs) restores rhythmic bursting activity to a previously paralyzed diaphragm within hours, days, or weeks following a C2 hemisection injury. Further, decreasing the excitability of V2a neurons impairs tonic diaphragm activity after injury as well as activation of inspiratory activity by chemosensory stimulation, but does not impact breathing at rest in healthy animals. By examining the patterns of muscle activity produced by modulating the excitability of V2a neurons, we provide evidence that V2a neurons supply tonic drive to phrenic circuits rather than increase rhythmic inspiratory drive at the level of the brainstem. Our results demonstrate that the V2a class of neurons contribute to recovery of respiratory function following injury. We propose that altering V2a excitability is a potential strategy to prevent respiratory motor failure and promote recovery of breathing following spinal cord injury.

EXPLORING THE IMPORTANCE OF DIAPHRAGM ACTIVATION, GLUTEAL ACTIVATION, AND THEIR EFFECTS ON GLUTEAL AMNESIA, PELVIC FLOOR ACTIVATION, CLINICAL PILATES FOR JOINTS CORE TRAINING AND PRECAUTIONS IN EXERCISE SELECTION

Clinical Pilates has emerged as a prominent therapeutic approach aimed at improving movement control, stability, and rehabilitation outcomes across diverse populations. This research article delves into the pivotal aspects of Clinical Pilates, shedding light on the significance of diaphragm activation, gluteal activation, and their intricate relationship with gluteal amnesia, pelvic floor activation, Pilates for joint health, exercise selection precautions, and core training strategies. Through a synthesis of relevant concepts and evidence-based insights, this article offers practical recommendations tailored for Pilates practitioners and healthcare professionals, illuminating the multifaceted nature of Clinical Pilates and its profound impact on musculoskeletal health and functional well-being.

Evaluation of patients with chronic obstructive pulmonary disease by maximal inspiratory pressure and diaphragmatic excursion with ultrasound sonography

BackgroundDecreased respiratory muscle strength and muscle mass is key in diagnosing respiratory sarcopenia. However, the role of reduced diaphragm activity, expressed as the maximal level of diaphragmatic excursion (DEmax), in diagnosing respiratory sarcopenia in patients with chronic obstructive pulmonary disease (COPD) remains unclear. This study aimed to characterize patients with COPD and low DEmax and maximal inspiratory pressure (MIP), a measure of inspiratory muscle strength, and assess the role of DEmax in respiratory sarcopenia. MethodsPatients with COPD underwent spirometry, exercise tolerance (VO2peak) test, and MIP measurement. DEmax and sternocleidomastoid thickness at the maximal inspiratory level (TscmMIL) were assessed using ultrasound sonography. ResultsOverall, 58 patients with COPD (median age, 76 years; median %FEV1, 51.3 %) were included, 28 of whom showed a %MIP of ≥80 %, defined as having preserved MIP. Based on the %MIP of 80 % and median value of DEmax (48.0 mm) as thresholds, the patients were stratified into four groups: both-high (n = 18), %MIP-alone low (n = 11), DEmax-alone low (n = 10), and both-low (n = 19) groups. The both-low group exhibited the lowest %FEV1, Δinspiratory capacity, VO2peak, and TscmMIL, and these values were significantly lower than those of the both-high group. Except for %FEV1, these values were significantly lower in the both-low group than in the %MIP-alone low group despite adjusting DEmax level for body mass index. ConclusionMeasuring DEmax along with MIP can characterize patients with COPD, reduced exercise capacity, and decreased accessory respiratory muscle mass and can help diagnose respiratory sarcopenia.

Asymmetrical high-flow nasal cannula performs similarly to standard interface in patients with acute hypoxemic post-extubation respiratory failure: a pilot study

BackgroundStandard high-flow nasal cannula (HFNC) is a respiratory support device widely used to manage post-extubation hypoxemic acute respiratory failure (hARF) due to greater comfort, oxygenation, alveolar recruitment, humidification, and reduction of dead space, as compared to conventional oxygen therapy. On the contrary, the effects of the new asymmetrical HFNC interface (Optiflow® Duet system (Fisher & Paykel, Healthcare, Auckland, New Zealand) is still under discussion. Our aim is investigating whether the use of asymmetrical HFNC interface presents any relevant difference, compared with the standard configuration, on lung aeration (as assessed by end-expiratory lung impedance (EELI) measured by electrical impedance tomography (EIT)), diaphragm ultrasound thickening fraction (TFdi) and excursion (DE), ventilatory efficiency (estimated by corrected minute ventilation (MV)), gas exchange, dyspnea, and comfort.MethodsPilot physiological crossover randomized controlled study enrolling 20 adults admitted to the Intensive Care unit, invasively ventilated for at least 24 h, and developing post-extubation hARF, i.e., PaO2/set FiO2 < 300 mmHg during Venturi mask (VM) within 120 min after extubation. Each HFNC configuration was applied in a randomized 60 min sequence at a flow rate of 60 L/min.ResultsGlobal EELI, TFdi, DE, ventilatory efficiency, gas exchange and dyspnea were not significantly different, while comfort was greater during asymmetrical HFNC support, as compared to standard interface (10 [7–10] and 8 [7–9], p-value 0.044).ConclusionsIn post-extubation hARF, the use of the asymmetrical HFNC, as compared to standard HFNC interface, slightly improved patient comfort without affecting lung aeration, diaphragm activity, ventilatory efficiency, dyspnea and gas exchange.Clinical trial numberClinicalTrial.gov. Registration number: NCT05838326 (01/05/2023).New & noteworthyThe asymmetrical high-flow nasal cannula oxygen therapy (Optiflow® Duet system (Fisher & Paykel, Healthcare, Auckland, New Zealand) provides greater comfort as compared to standard interface; while their performance in term of lung aeration, diaphragm activity, ventilatory efficiency, dyspnea, and gas exchange is similar.

Evaluation and modeling of diaphragm displacement using ultrasound imaging for wearable respiratory assistive robot.

Assessing the influence of respiratory assistive devices on the diaphragm mobility is essential for advancing patient care and improving treatment outcomes. Existing respiratory assistive robots have not yet effectively assessed their impact on diaphragm mobility. In this study, we introduce for the first time a non-invasive, real-time clinically feasible ultrasound method to evaluate the impact of soft wearable robots on diaphragm displacement. We measured and compared diaphragm displacement and lung volume in eight participants during both spontaneous and robotic-assisted respiration. Building on these measurements, we proposed a human-robot coupled two-compartment respiratory mechanics model that elucidates the underlying mechanism by which our extracorporeal wearable robots augments respiration. Specifically, the soft robot applies external compression to the abdominal wall muscles, inducing their inward movement, which consequently pushes the diaphragm upward and enhances respiratory function. Finally, we investigated the level and shape of various robotic assistive forces on diaphragm motion. This robotic intervention leads to a significant increase in average diaphragm displacement by 1.95 times and in lung volume by 2.14 times compared to spontaneous respiration. Furthermore, the accuracy of the proposed respiratory mechanics model is confirmed by the experimental results, with less than 7% error in measurements of both diaphragm displacement and lung volume. Finally, the magnitude of robotic assistive forces positively correlates with diaphragm movement, while the shape of the forces shows no significant relationship with diaphragm activity. Our experimental findings validate the effective assistance mechanism of the proposed robot, which enhances diaphragm mobility and assists in ventilation through extracorporeal robotic intervention. This robotic system can assist with ventilation while increasing diaphragm mobility, potentially resolving the issue of diaphragm atrophy. Additionally, this work paves the way for improved robotic designs and personalized assistance, tailored to the dynamics of the diaphragm in respiratory rehabilitation.

Comparative Effect of High-Frequency Nasal Cannula and Noninvasive Ventilation on the Work of Breathing and Postoperative Pulmonary Complication after Pediatric Congenital Cardiac Surgery: A Prospective Randomized Controlled Trial.

Various forms of commonly used noninvasive respiratory support strategies have considerable effect on diaphragmatic contractile function which can be evaluated using sonographic diaphragm activity parameters. To compare the magnitude of respiratory workload decreased as assessed by thickening fraction of the diaphragm and longitudinal diaphragmatic strain while using high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) modes [nasal intermittent positive pressure ventilation (NIPPV) and bilevel positive airway pressure (BiPAP)] in pediatric patients after cardiothoracic surgery. This prospective randomized controlled trial was performed at a tertiary care surgical intensive care unit in postcardiac surgery patients aged between 1 and 48 months, who were randomly allocated into three groups: 1) HFNC (with flows at 2 L/kg/min), 2) NIPPV via RAMS cannula in PSV mode (pressure support 8 cmH2O, PEEP 5 cmH2O), and 3) BiPAP in nCPAP mode (CPAP of 5 cmH2O). Measurements were recorded at baseline after extubation (R0) and subsequently every 12 hourly (R1, R2, R3, R4, R5) at 12, 24, 36, 48, and 60 hours respectively until therapy was discontinued. Sixty patients were included, with 20 patients each in the NIPPV group, HFNC group, and BiPAP group. Longitudinal strain at crura of diaphragm was lower in the BiPAP group as compared to HFNC group at R2-R4 [R2 (-4.27± -2.73 vs - 8.40± -6.40, P = 0.031), R3 (-5.32± -2.28 vs -8.44± -5.6, P = 0.015), and R4 (-3.8± -3.42 vs -12.4± -7.12, P = 0.040)]. PFR was higher in HFNC than NIPPV group at baseline and R1-R3[R0 (323 ± 114 vs 264 ± 80, P = 0.008), R1 (311 ± 114 vs 233 ± 66, P = 0.022), R2 (328 ± 116 vs 237 ± 4, P = 0.002), R3 (346 ± 112 vs 238 ± 54, P = 0.001)]. DTF and clinical parameters of increased work of breathing remain comparable between three groups. The rate of reintubation (within 48 hours of extubation or at ICU discharge) was 0.06% (1 in NIPPV, 1 in BiPAP, 2 in HFNC) and remain comparable between groups (P = 1.0). BiPAP may provide better decrease in work of breathing compared to HFNC as reflected by lower crural diaphragmatic strain pattern. HFNC may provide better oxygenation compared to NIPPV group, as reflected by higher PFR ratio. Failure rate and safety profile are similar among different methods used.

Divergent expiratory braking activity of costal and crural diaphragm

BackgroundThere is increasing clinical interest in understanding the contribution of the diaphragm in early expiration, especially during mechanical ventilation. However, current experimental evidence is limited, so essential activity of the diaphragm during expiration and diaphragm segmental differences in expiratory activity, are unknown. ObjectivesTo determine if: 1) the diaphragm is normally active into expiration during spontaneous breathing and hypercapnic ventilation, 2) expiratory diaphragmatic activity is distributed equally among the segments of the diaphragm, costal and crural. MethodsIn 30 spontaneously breathing male and female canines, awake without confounding anesthetic, we measured directly both inspiratory and expiratory electrical activity (EMG), and corresponding mechanical shortening, of costal and crural diaphragm, during room air and hypercapnia. ResultsDuring eupnea, costal and crural diaphragm are active into expiration, showing significant and distinct expiratory activity, with crural expiratory activity greater than costal, for both magnitude and duration. This diaphragm segmental difference diverged further during progressive hypercapnic ventilation: crural expiratory activity progressively increased, while costal expiratory activity disappeared. ConclusionThe diaphragm is not passive during expiration. During spontaneous breathing, expiratory activity -“braking”- of the diaphragm is expressed routinely, but is not equally distributed. Crural muscle “braking” is greater than costal muscle in magnitude and duration.With increasing ventilation during hypercapnia, expiratory activity -“braking”- diverges notably. Crural expiratory activity greatly increases, while costal expiratory “braking” decreases in magnitude and duration, and disappears.Thus, diaphragm expiratory "braking" action represents an inherent, physiological function of the diaphragm, distinct for each segment, expressing differing neural activation.

Noninvasive Neurally Adjusted Ventilation versus Nasal Continuous or Intermittent Positive Airway Pressure for Preterm Infants: A Systematic Review and Meta-Analysis.

The noninvasive neurally adjusted ventilatory assist (NIV-NAVA) is a newly developed noninvasive ventilation technique with promising clinical and ventilatory outcomes for preterm infants. This systematic review and meta-analysis aimed to investigate whether NIV-NAVA has better clinical and ventilatory outcomes than nasal continuous airway pressure (NCPAP) or noninvasive positive pressure ventilation (NIPP) on premature infants. MEDLINE, Embase, and CENTRAL were searched, and randomized controlled trials (RCTs) that compared NIV-NAVA with NCPAP or NIPP for preterm infants (gestational age: <37 weeks) were included. We evaluated the following outcomes in the neonatal intensive care unit: the desaturation rate, failure of noninvasive modality requiring intubation when received as the primary mode or the need for re-intubation after extubation from mechanical ventilation in the secondary mode (weaning), length of stay, and fraction of inspired oxygen. The mean difference and risk ratio were used to represent continuous and dichotomous outcomes, respectively. We included nine RCTs involving 339 preterm infants overall. NIV-NAVA showed similar clinical and ventilatory outcomes to NCPAP or NIPP, except for the maximum diaphragmatic electrical activity. The rate of failure of the noninvasive modality was not statistically different between NIV-NAVA and NCPAP. The pooled estimates for the maximum electrical activity were significantly reduced in NIV-NAVA compared with those in NIPP. The findings suggest that NIV-NAVA may be as safe and effective as NCPAP and NIPP for preterm neonates, particularly those who may not tolerate these alternative noninvasive methods. However, further trials are recommended for greater evidence.

Noninvasive Neurally Adjusted Ventilatory Assist in Infants With Bronchiolitis: Respiratory Outcomes in a Single-Center, Retrospective Cohort, 2016-2018.

To describe our experience of using noninvasive neurally adjusted ventilatory assist (NIV-NAVA) in infants with bronchiolitis, its association with the evolution of respiratory effort, and PICU outcomes. Retrospective analysis of a prospectively curated, high-frequency electronic database. A PICU in a university-affiliated maternal-child health center in Canada. Patients younger than 2 years old who were admitted with a diagnosis of acute bronchiolitis and treated with NIV-NAVA from October 2016 to June 2018. None. Patient characteristics, as well as respiratory and physiologic parameters, including electrical diaphragmatic activity (Edi), were extracted from the electronic database. Respiratory effort was estimated using the modified Wood Clinical Asthma Score (mWCAS) and the inspiratory Edi. A comparison in the respiratory effort data was made between the 2 hours before and 2 hours after starting NIV-NAVA. In the two seasons, 64 of 205 bronchiolitis patients were supported with NIV-NAVA. These 64 patients had a median (interquartile range [IQR]) age of 52 days (32-92 d), and there were 36 of 64 males. Treatment with NIV-NAVA was used after failure of first-tier noninvasive respiratory support; 25 of 64 patients (39%) had at least one medical comorbidity. NIV-NAVA initiation was associated with a moderate decrease in mWCAS from 3.0 (IQR, 2.5-3.5) to 2.5 (IQR, 2.0-3.0; p < 0.001). NIV-NAVA initiation was also associated with a statistically significant decrease in Edi ( p < 0.01). However, this decrease was only clinically relevant in infants with a 2-hour baseline Edi greater than 20 μV; here, the before and after Edi was 44 μV (IQR, 33-54 μV) compared with 27 μV (IQR, 21-36 μV), respectively ( p < 0.001). Overall, six of 64 patients (9%) required endotracheal intubation. In this single-center retrospective cohort, in infants with bronchiolitis who were considered to have failed first-tier noninvasive respiratory support, the use of NIV-NAVA was associated with a rapid decrease in respiratory effort and a 9% intubation rate.

Closed-loop cervical epidural stimulation partially restores ipsilesional diaphragm EMG after acute C2 hemisection

Cervical spinal cord injury creates lasting respiratory deficits which can require mechanical ventilation long-term. We have shown that closed-loop epidural stimulation (CL-ES) elicits respiratory plasticity in the form of increased phrenic network excitability (Malone et. al., E Neuro, Vol 9, 0426–21.2021, 2022); however, the ability of this treatment to create functional benefits for breathing function per se after injury has not been demonstrated. Here, we demonstrate in C2 hemisected anesthetized rats, a 20-minute bout of CL-ES administered at current amplitudes below the motor threshold restores paralyzed hemidiaphragm activity in-phase with breathing while potentiating contralesional activity. While this acute bout of stimulation did not elicit the increased network excitability seen in our chronic model, a subset of stimulated animals continued spontaneous ipsilesional diaphragm activity for several seconds after stopping stimulation. These results support the use of CL-ES as a therapeutic to rescue breathing after high cervical spinal cord injury, with the potential to lead to lasting recovery and device independence.

Phrenic Nerve Stimulation for Acute Respiratory Failure.

Diaphragm inactivity during invasive mechanical ventilation leads to diaphragm atrophy and weakness, hemodynamic instability, and ventilatory heterogeneity. Absent respiratory drive and effort can, therefore, worsen injury to both lung and diaphragm and is a major cause of failure to wean. Phrenic nerve stimulation (PNS) can maintain controlled levels of diaphragm activity independent of intrinsic drive and as such may offer a promising approach to achieving lung and diaphragm protective ventilatory targets. Whereas PNS has an established role in the management of chronic respiratory failure, there is emerging interest in how its multisystem putative benefits may be temporarily harnessed in the management of invasively ventilated patients with acute respiratory failure.

Physiological effects of high-flow nasal cannula oxygen therapy after extubation: a randomized crossover study

BackgroundProphylactic high-flow nasal cannula (HFNC) oxygen therapy can decrease the risk of extubation failure. It is frequently used in the postextubation phase alone or in combination with noninvasive ventilation. However, its physiological effects in this setting have not been thoroughly investigated. The aim of this study was to determine comprehensively the effects of HFNC applied after extubation on respiratory effort, diaphragm activity, gas exchange, ventilation distribution, and cardiovascular biomarkers.MethodsThis was a prospective randomized crossover physiological study in critically ill patients comparing 1 h of HFNC versus 1 h of standard oxygen after extubation. The main inclusion criteria were mechanical ventilation for at least 48 h due to acute respiratory failure, and extubation after a successful spontaneous breathing trial (SBT). We measured respiratory effort through esophageal/transdiaphragmatic pressures, and diaphragm electrical activity (ΔEAdi). Lung volumes and ventilation distribution were estimated by electrical impedance tomography. Arterial and central venous blood gases were analyzed, as well as cardiac stress biomarkers.ResultsWe enrolled 22 patients (age 59 ± 17 years; 9 women) who had been intubated for 8 ± 6 days before extubation. Respiratory effort was significantly lower with HFNC than with standard oxygen therapy, as evidenced by esophageal pressure swings (5.3 [4.2–7.1] vs. 7.2 [5.6–10.3] cmH2O; p < 0.001), pressure–time product (85 [67–140] vs. 156 [114–238] cmH2O*s/min; p < 0.001) and ΔEAdi (10 [7–13] vs. 14 [9–16] µV; p = 0.022). In addition, HFNC induced increases in end-expiratory lung volume and PaO2/FiO2 ratio, decreases in respiratory rate and ventilatory ratio, while no changes were observed in systemic hemodynamics, Troponin T, or in amino-terminal pro-B-type natriuretic peptide.ConclusionsProphylactic application of HFNC after extubation provides substantial respiratory support and unloads respiratory muscles.Trial registration January 15, 2021. NCT04711759.

Cardiorespiratory monitoring with a wireless and nonadhesive belt measuring diaphragm activity in preterm and term infants: A multicenter non-inferiority study.

We determined if the heart rate (HR) monitoring performance of a wireless and nonadhesive belt is non-inferior compared to standard electrocardiography (ECG). Secondary objective was to explore the belt's respiratory rate (RR) monitoring performance compared to chest impedance (CI). In this multicenter non-inferiority trial, preterm and term infants were simultaneously monitored with the belt and conventional ECG/CI for 24 h. HR monitoring performance was estimated with the HR difference and ability to detect cardiac events compared to the ECG, and the incidence of HR-data loss per second. These estimations were statistically compared to prespecified margins to confirm equivalence/non-inferiority. Exploratory RR analyses estimated the RR trend difference and ability to detect apnea/tachypnea compared to CI, and the incidence of RR-data loss per second. Thirty-nine infants were included. HR monitoring with the belt was non-inferior to the ECG with a mean HR difference of 0.03 beats per minute (bpm) (standard error [SE] = 0.02) (95% limits of agreement [LoA]: [-5 to 5] bpm) (p < 0.001). Second, sensitivity and positive predictive value (PPV) for cardiac event detection were 94.0% (SE = 0.5%) and 92.6% (SE = 0.6%), respectively (p ≤ 0.001). Third, the incidence of HR-data loss was 2.1% (SE = 0.4%) per second (p < 0.05). The exploratory analyses of RR showed moderate trend agreement with a mean RR-difference of 3.7 breaths/min (SE = 0.8) (LoA: [-12 to 19] breaths/min), but low sensitivities and PPV's for apnea/tachypnea detection. The incidence of RR-data loss was 2.2% (SE = 0.4%) per second. The nonadhesive, wireless belt showed non-inferior HR monitoring and a moderate agreement in RR trend compared to ECG/CI. Future research on apnea/tachypnea detection is required.

Physiological responses during static apnoea efforts in elite and novice breath-hold divers before and after two weeks of dry apnoea training

This study examined the effect of breath-hold (BH) training on apnoeic performance in novice BH divers (NBH:n = 10) and compared them with data from elite BH divers (EBH:n = 11). Both groups performed 5-maximal BHs (PRE). The NBH group repeated this protocol after two weeks of BH training (POST). The NBH group during BH efforts significantly increased red blood cell concentration (4.56 ± 0.16Mio/μl) by 5.06%, hemoglobin oxygen saturation steady state duration (110.32 ± 29.84 s) by 15.48%, and breath-hold time (BHT:144.19 ± 47.35 s) by 33.77%, primarily due to a 59.70% increase in struggle phase (71.85 ± 30.89 s), in POST. EBH group exhibited longer BHT (283.95 ± 36.93 s) and struggle-phase (150.10 ± 34.69 s) than NBH (POST). Elite divers recorded a higher peak MAP (153.18 ± 12.28 mmHg) compared to novices (PRE:123.70 ± 15.65 mmHg, POST:128.30 ± 19.16 mmHg), suggesting that a higher peak MAP is associated with a better BHT. The concurrent abrupt increase of diaphragmatic activity and MAP, seen only in the EBH group, suggests a potential interaction. Additionally, apnoea training increases red blood cells concentration in repeated apnoea efforts and increases BH stamina.

Modulatory effect of trans-spinal magnetic intermittent theta burst stimulation on diaphragmatic activity following cervical spinal cord contusion in the rat

Background CONTEXTMagnetic stimulation can noninvasively modulate the neuronal excitability through different stimulatory patterns. PurposeThe present study hypothesized that trans-spinal magnetic stimulation with intermittent theta burst stimulatory pattern can modulate respiratory motor outputs in a pre-clinical rat model of cervical spinal cord injury. Study designIn vivo animal study. MethodsThe effect of trans-spinal magnetic intermittent theta burst stimulation on diaphragmatic activity was assessed in adult rats with unilateral cervical spinal cord contusion at 2 weeks postinjury. ResultsThe results demonstrated that unilateral cervical spinal cord contusion significantly attenuated the inspiratory activity and motor evoked potential of the diaphragm. Trans-spinal magnetic intermittent theta burst stimulation significantly increased the inspiratory activity of the diaphragm in cervical spinal cord contused rats. Inspiratory bursting was also recruited by trans-spinal magnetic intermittent theta burst stimulation in the rats without diaphragmatic activity after cervical spinal cord injury. In addition, trans-spinal magnetic intermittent theta burst stimulation is associated with increases in oxygen consumption and carbon dioxide production. ConclusionsThese results suggest that trans-spinal magnetic intermittent theta burst stimulation can induce respiratory neuroplasticity. Clinical significanceWe propose that trans-spinal theta burst magnetic stimulation may be considered a potential rehabilitative strategy for improving the respiratory activity after cervical spinal cord injury. This will require future clinical study.

Diaphragm function in patients with Covid-19-related acute respiratory distress syndrome on venovenous extracorporeal membrane oxygenation

BackgroundVenovenous extracorporeal membrane oxygenation (VV ECMO) is frequently associated with deep sedation and neuromuscular blockades, that may lead to diaphragm dysfunction. However, the prevalence, risk factors, and evolution of diaphragm dysfunction in patients with VV ECMO are unknown. We hypothesized that the prevalence of diaphragm dysfunction is high and that diaphragm activity influences diaphragm function changes.MethodsPatients with acute respiratory distress syndrome (ARDS) requiring VV ECMO were included in two centers. Diaphragm function was serially assessed by measuring the tracheal pressure in response to phrenic nerve stimulation (Ptr,stim) from ECMO initiation (Day 1) until ECMO weaning. Diaphragm activity was estimated from the percentage of spontaneous breathing ventilation and by measuring the diaphragm thickening fraction (TFdi) with ultrasound.ResultsSixty-three patients were included after a median of 4 days (3–6) of invasive mechanical ventilation. Diaphragm dysfunction, defined by Ptr, stim ≤ 11 cmH2O, was present in 39 patients (62%) on Day 1 of ECMO. Diaphragm function did not change over the study period and was not influenced by the percentage of spontaneous breathing ventilation or the TFdi during the 1 week. Among the 63 patients enrolled in the study, 24 (38%) were still alive at the end of the study period (60 days).ConclusionsSixty-two percent of patients undergoing ECMO for ARDS related to SARS CoV-2 infection had a diaphragm dysfunction on Day 1 of ECMO initiation. Diaphragm function remains stable over time and was not associated with the percentage of time with spontaneous breathing.ClinicalTrials.gov Identifier NCT04613752 (date of registration February 15, 2021).

Diaphragmatic electromyography in infants: an overview of possible clinical applications.

Preterm infants often experience breathing instability and a hampered lung function. Therefore, these infants receive cardiorespiratory monitoring and respiratory support. However, the current respiratory monitoring technique may be unreliable for especially obstructive apnea detection and classification and it does not provide insight in breathing effort. The latter makes the selection of the adequate mode and level of respiratory support difficult. Electromyography of the diaphragm (dEMG) has the potential of monitoring heart rate (HR) and respiratory rate (RR), and it provides additional information on breathing effort. This review summarizes the available evidence on the clinical potential of dEMG to provide cardiorespiratory monitoring, to synchronize patient-ventilator interaction, and to optimize the mode and level of respiratory support in the individual newborn infant. We also try to identify gaps in knowledge and future developments needed to ensure widespread implementation in clinical practice. IMPACT: Preterm infants require cardiorespiratory monitoring and respiratory support due to breathing instability and a hampered lung function. The current respiratory monitoring technique may provide unreliable measurements and does not provide insight in breathing effort, which makes the selection of the optimal respiratory support settings difficult. Measuring diaphragm activity could improve cardiorespiratory monitoring by providing insight in breathing effort and could potentially have an important role in individualizing respiratory support in newborn infants.